Fuchimoto S, Yasui Y, Gouchi A, Hamada F, Sanada E, Urakubo M, Okura M, Akamatsu Y, Sasaki A, Orita K
Dept. of Surgery, Okayama University Medical School.
Gan To Kagaku Ryoho. 1988 Aug;15(8 Pt 2):2396-400.
The objectives in administering anti-cancer therapeutics to the feeding artery of the tumor are to allow the agent to come in direct contact with the tumor cells, to lower the concentration of the agent in body circulation, to lessen the severity of side effects, and to augment efficacy of the agent. A remarkable partial regression was observed in two patients with advanced hepatocellular carcinoma, both at the stage in which surgical excision was diagnosed impossible; one was given successive and daily bolus administration of OH-1, a anti-tumor agent consisting of natural human tumor necrosis factor-alpha (nHuTNF-alpha) and natural human interferon (nHulFN-alpha), and the other a successive and daily combined bolus administration of OH-1 and 5-FU. On investigating the role of the anti-cancer activity of OH-1 by analyzing the NK activity of rat liver large granular lymphocytes, we found that the NK activity was suppressed dose-dependently by nHuTNF-alpha, but not significantly. Thus, an increase in TNF dose in hepatic artery therapy seems undesirable from the standpoint of NK activity. The authors are presently carrying out investigations to elucidate the effector mechanism of the anticancer activity of OH-1.
将抗癌治疗药物注入肿瘤供血动脉的目的是使药物与肿瘤细胞直接接触,降低药物在体循环中的浓度,减轻副作用的严重程度,并提高药物的疗效。在两名晚期肝细胞癌患者中观察到显著的部分缓解,这两名患者均处于被诊断无法进行手术切除的阶段;其中一名患者连续每日给予OH-1推注,OH-1是一种由天然人肿瘤坏死因子-α(nHuTNF-α)和天然人干扰素(nHulFN-α)组成的抗肿瘤药物,另一名患者连续每日给予OH-1和5-FU联合推注。通过分析大鼠肝大颗粒淋巴细胞的NK活性来研究OH-1抗癌活性的作用时,我们发现NK活性被nHuTNF-α剂量依赖性抑制,但不显著。因此,从NK活性的角度来看,肝动脉治疗中增加TNF剂量似乎不可取。作者目前正在进行研究以阐明OH-1抗癌活性的效应机制。